Figure 9.

Simulation of Piezo1 channel kinetics by the modified four-state gating model. (a) A schematic of the modified four-state gating mechanism for Piezo1, with arrows indicating transitions between open (O), closed (C) and two inactivated states (I₁ and I₂). In the original model, $a\left(\mathrm{\tau }\right)\mathrm{and}e(\mathrm{\tau })$ are coupling coefficients between C, O and I₁ states, respectively, which are modulated by the pressure (or equivalently $\mathrm{\tau }$ in this study) applied to the plasma membrane, leading to membrane tension. Moreover, g and h are the coupling coefficients between O and I₂ states, which are constants. In the modified model, g (PL) and h (PL) are assumed to be PL-dependent while the rest of the coefficients are the same as in the original model. (b) The peak probability of the O, I₁ and I₂ evoked by the 1^st pulse at various PL. (c) The peak probability of the O, I₁ and I₂ evoked by the last pulse at various PL. (d–f) The normalized shear stress (red), simulated Piezo1 open (blue), closed (magenta), inactivation 1 (black) and inactivation 2 (green) probabilities change in response to 60 s insonification for PL = 1, 20 and 1000 ms, respectively. (d1–f1) The magnified plot at the beginning of the insonification for PL = 1, 20 and 1000 ms, respectively. (d2–f2) The magnified plot toward the end of the insonification for PL = 1, 20 and 1000 ms, respectively.